13 Jun 2024

Research blog: How leukaemia cells thrive

In February 2024, a ground-breaking study was published in the esteemed journal Nature Communications (i), showcasing collaborative research efforts from a team of scientists, including three of our current and previously funded researchers Dr Sophie G. Kellaway, Dr Sandeep Potluri, and Dr Daniel J. L. Coleman. Their research focused on the pathways that lead to relapse in acute myeloid leukaemia – a significant hurdle in treatment.

Acute myeloid leukaemia (AML) is like a disruption in the orchestra of blood cell development, caused by genetic mutations. These mutations throw off the rhythm of normal growth, leading to the rapid multiplication of immature cells called blast cells. If left unchecked, these blast cells can overwhelm the body and become life-threatening.

While chemotherapy serves as the main treatment, it’s a bit like playing whack-a-mole—it can’t always catch all the leukaemia cells. Among those that escape are sneaky ones known as leukemic stem cells (LSCs). These crafty cells can lie low during treatment, only to spring back to life later on, causing a relapse.

But the big question remains: How do these cells manage to pull off their vanishing act and then reappear?

The study delves into how LSC’s in a subtype of acute myeloid leukaemia (AML), called t(8;21), restart their growth – causing relapse. The LSCs manage to cheat death by activating VEGF (vascular endothelial growth factor – this is a powerful factor that helps blood vessels grow) and IL-5 (these usually lead to maintenance of survival and functions of B cells and eosinophils – white blood cells) signalling pathways in an abnormal manner.

This finding is fascinating, it’s as if they’re flipping switches to turn on growth-promoting signals. And they don’t go solo—these pathways team up with certain proteins to coordinate the revival of LSCs while also ensuring they can keep renewing themselves.

It’s like they’ve cracked the code for eternal youth, but in a dangerous way. Understanding this intricate dance between LSCs and their signalling pathways could be the key to designing smarter treatments that target these pathways directly, aiming to cut off their supply lines and prevent leukaemia from making a comeback.

In conclusion, the recent study sheds light on the complex mechanisms underlying relapse in AML, uncovering how LSCs manage to reignite their growth. Understanding these processes is pivotal for developing targeted treatments that can intercept these pathways and halt relapse. This underscores the importance of continued support and funding for leukaemia research, as unravelling these mysteries is key to unlocking more effective therapies and ultimately stopping leukaemia in its tracks.

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References:

(i) – Kellaway SG, Potluri S, Keane P, Blair HJ, Ames L, Worker A, Chin PS, Ptasinska A, Derevyanko PK, Adamo A, Coleman DJL, Khan N, Assi SA, Krippner-Heidenreich A, Raghavan M, Cockerill PN, Heidenreich O, Bonifer C. Leukemic stem cells activate lineage inappropriate signalling pathways to promote their growth. Nat Commun. 2024 Feb 14;15(1):1359. doi: 10.1038/s41467-024-45691-4. PMID: 38355578; PMCID: PMC10867020.